International Journal of Contemporary Pediatrics Balasankar S et al. Int J Contemp Pediatr. 2017 Jul;4(4):1236-1239 http://www.ijpediatrics.com pISSN 2349-3283 | eISSN 2349-3291

DOI: http://dx.doi.org/10.18203/2349-3291.ijcp20172564 Original Research Article

A study on validity of reading Mantoux test at 24 hours

Soundaiyan Balasankar, Jeyaraman Balasubramanian*

Department of Pediatrics, Institute of Child Health and Research Centre, Government Rajaji Hospital, Madurai Medical College, Madurai, Tamil Nadu, India

Received: 08 May 2017 Accepted: 29 May 2017

*Correspondence: Dr. Jeyaraman Balasubramanian, E-mail: [email protected]

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Tuberculosis (TB) is a chronic infectious disease caused by mycobacterium tuberculosis and one of the major disease affecting children throughout the world. Prevalence of active disease in adults in India is 18 per 1000 population. The aim of the current study was to see whether reading Mantoux test at 24 hours can predict Mantoux positivity at 48 hours. Methods: A Prospective observational study was conducted in Tertiary care hospital which caters for people in and around Madurai, Tamil Nadu, India. Total 6560 children in the age group of 6 months to 12 years with suspicion of Tuberculosis. (Positive contact history or Low weight for age or persistent fever for more than 2 weeks or cough for more than two weeks or significant lymphadenopathy) were given Mantoux test. Of these 5904 (90%) children turned up for 24hours and 48 hours reading. Transverse diameter of the induration was measured. More than 10mm was considered as Mantoux positivity. The size of induration at 24 hours and 48 hours were compared. Results: Out of 5904 children, 206 (3.48%) children had Mantoux positivity at 48 hours. Of these 206 children, 131 (63.6%) children had more than 10 mm at 24 hours. Remaining 75 (36.4) showed less than 10 mm at 24 hours, but become more than >10 mm at 48 hours. Overall tuberculin positivity is 3.5%. Conclusions: Positivity of tuberculin test must be confirmed at 48 hours only. There is no standard reading at 24 hours which can be presumed to become positive at 48 hours.

Keywords: Childhood tuberculosis, Mantoux test, Purified protein derivative

INTRODUCTION Diagnosis of TB is still a tough task in children. Tuberculin skin test (Mantoux test) using Tuberculin- Tuberculosis (TB) is a chronic infectious disease caused PPD RT23 still plays a major role especially in children. by mycobacterium tuberculosis and one of the major disease affecting children throughout the world. Conventionally Mantoux reading is done at 48-72 hours Prevalence of active disease in adults in India is 18 per only. Some patients may find it difficult to come back 1000 population.1 In children, the clinical features are after 2 days and may be willing to come back the next vague and non-specific. Symptoms include low grade day. A few patients may not turn up to the physician once fever for >2 weeks, loss of appetite, poor weight gain, the symptoms for which they seek medical advice recent weight loss, night sweats, dry cough of >2 weeks, resolves. significant lymphadenopathy. About 25-35% have an extra pulmonary presentation. Ratio of pulmonary to Thus a few Mantoux tests go unread. Reading Mantoux at extra pulmonary TB is 3:1.2 24 hours itself can bring down this dropout rate. With

International Journal of Contemporary Pediatrics | July-August 2017 | Vol 4 | Issue 4 Page 1236 Balasankar S et al. Int J Contemp Pediatr. 2017 Jul;4(4):1236-1239 these aspects in mind, this study was done with an aim to cases (3.48%) reading was more than 10 mm at 48 hours find out whether reading Mantoux at 24 hours can predict and were considered Mantoux positive. positivity at 48 hours. Table 1: Age distribution of 206 positive cases. METHODS Cases Age group This prospective observational study was conducted in No. % the Institute of Child Health and Research Centre, <1 year 9 4.4 Government Rajaji Hospital, Madurai, Tamil Nadu, India 1-5 years 90 43.7 after obtaining informed consent from the care givers. 5-10 years 82 39.8 The study enrolled 6560 children between 6 months to 12 >10 years 25 12.1 years age group with any of the following features. Total 206 100 • Positive contact history Range 11 months – 12 years • Low weight for age (<80% of expected/recent weight Mean 6.1 years loss of 10%) S.D. 3.2 years • Persistent fever for >2 weeks • Persistent cough for >2 weeks Table 2: Induration values at various time intervals • Significant lymphadenopathy for 206 positive cases.

Children with recent vaccination, recent viral illness, Time interval (hours) prior Mantoux positivity were excluded. Induration (mm) 24 48 No. % No. % SPAN’s tuberculin PPD (Code NO: 18411) was used in 0 5 2.4 - - current study. It is a diluted and ready to use solution for 1-4 6 2.9 - - performing Mantoux test. Source material is calibrated against batch RT23 manufactured by Staten’s Serum 5-9 64 31.1 - - Institute, Denmark. It is diluted with a buffer containing 10 and above 131 63.6 206 100 Tween-80 as a stabilizer. Total 206 100 206 100 Range 0-30 0 - 40 All children were given 0.1 ml of 1TU PPD intradermally Mean 11.53 16.61 over the mid-volar aspect of left forearm using tuberculin SD 5.11 3.85 syringe after cleansing the area with spirit. Plastic p 0.0001 (significant) disposable Tuberculin syringe with 27-gauge needle was 3 used. The skin of the arm is lightly stretched lengthwise This Table shows age wise distribution of patients. and the pointer of the needle is inserted lengthwise, with Among the 206 positive cases, 131 cases (63.6%) had bevel upward, intradermally. After injection, appearance induration >10 mm at 24 hours, 64 cases (31.1%) were of a pale wheal of 6-10 mm was taken as correct between 5-9 mm at 24 hours, 6 cases (2.9%) were intradermal administration. Care givers and children were between 1-4 mm and only 5 cases (2.4%) had no educated not to wipe/scrub/massage/apply cream over the induration at 24 hours. test site. They were specially advised about the importance of reporting at 24 hours and 48 hours for Table 3: Comparison of results at 24 hours with reading the test. 24 hours and at 48 hours readings were results at 48 hours for all cases. taken in all cases that turned-up for reading. Transverse diameter of the induration was palpated and marked by 24 hours induration Ball point pen technique (sokal method) and measured 48 hours induration with a transparent ruler in mm by the same observer in all ≥10 mm <10 mm cases.4 ≥10 mm 131 75 <10 mm 0 5698 Data was collected on pretested proforma with clinical True positive 131 details. False positive Nil True negative 5698 RESULTS False negative 75 Sensitivity 63.5% Baseline data Specificity 100% Positive predictive value 100% 6560 children with clinical suspicion of tuberculosis were Negative predictive value 98.7 % given Mantoux test. Among them, 5904 cases (90%) turned up for reading at 24 hours and 48 hours. In 206

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On comparing 24 hours reading to 48 hours reading, it children with symptoms suggestive of tuberculosis was observed that sensitivity was 63.5%, specificity and infection. PPV was 100% and NPV was 98.7%. In a study at Pondicherry among healthy school children, Among the 5904 cases, 131 cases had >10 mm at 24 18.4% were found to be tuberculin positive.7 In India, the hours compared to 206 cases at 48 hours 634 cases were overall prevalence of tuberculin reactivity in adults is about 30%; males 35% and females 25% as shown in the Table 4: Induration values for all cases at survey conducted by the National Tuberculosis Institute, various time intervals. Bangalore.8 In our study among the 206 positive cases, 105 cases (51%) are male and 101 (49%) are female. Time interval (hours) There is no significant difference in Mantoux positivity Induration (mm) based on sex of the children. 24 48

No. % No. % In a study by Oztwik to evaluate the predictive value of a 0-4 5139 87.0 5203 88.1 24 hours induration, the mean (SD) size of the induration 5-9 765 10.8 701 8.4 at 24 hours was less than that of the induration present at 10 and above 131 2.2 206 3.5 48 and 72 hours.9 Differences were statistically Total 5904 100 5904 100 significant (p <0.001). There was no difference between Range 0-30 0-40 48 and 72 hours reading (p >0.5). Mean 2.37 2.39 SD 2.89 3.39 In present study, the mean size of induration at 24 hours p 0.0014 (significant) (11.53) was less than that of induration present at 48 hours (16.61) with a significant p value (P=0.0001). The between 5-9 mm at 24 hours compared to 495 cases at 48 difference was significant especially when the induration hours. 5139 cases were between 0-4 mm at 24 hours at 24 hours was between 0-9 mm and there is little compared to 5203 cases at 48 hours. So, if Mantoux is difference when the induration was more than 10 mm at positive by >10 mm at 24 hours, it remains as positive 24 hours. In a study at Pondicherry among healthy school (>10mm) at 48 hours also. But, Mantoux readings children, the positive and negative predictive value for between 5-9 mm at 24 hours, does not show any relation induration >10 mm at 24 hours was estimated at 96.7 and 7 to Mantoux positivity at 48 hours. It shows if the 99.5% respectively. Even in children who had a reaction induration is <5 mm at 24 hours, it is less likely to of 0-9 mm at 24 hours, the tendency to remain negative become positive (>10 mm) after 48 hours. was very high as indicated by the positive and negative predictive values of 98.5% and 96.7% respectively. DISCUSSION In a study by Oztwik to evaluate the predictive value of a The tuberculin skin test has been the traditional method 24 hour induration, any induration 24 hours after placement of the tuberculin test had a sensitivity of 94% of diagnosing infection with mycobacterium tuberculosis. 9 The decision to select one test over the other depends and' a specificity of 75%. At 24 hours, induration of any upon the population to be tested, purpose of testing and size had a relatively low positive predictive value (63%), resource availability. The skin test only measures the although induration >5 mm had a higher (86%) positive degree of hypersensitivity and not immunity to predictive value and also demonstrated that it will not tuberculosis. The larger the reaction, greater is the always be possible to tell whether any induration (>5 probability that the responsible organism is M. mm) will develop into a positive test but if there is no tuberculosis. Tuberculin skin test is useful in the induration especially in children, it is highly possible evaluation of children suspected of having tuberculosis (98%) that the tuberculin test will be negative. that a significant reaction supports the diagnosis. In present study, it is found that on comparing 24 hours The health-care provider should inform the patient of the reading to 48 hours Mantoux reading it was observed that need to return for the reading of the test. Self-reading of sensitivity was 63.5, specificity and PPV was 100 and the test has been shown to be unreliable as said by APIC NPV was 98.7%. There is no. of false positivity and the guidelines committee about the responsibility for reading percentage of false negative is 75. If the induration is <5 the tuberculin skin test.5 In our study, among the 6560 mm at 24 hours, it is unlikely to become positive (>10 cases, 5904 cases (90%) only turned for reading at both mm) at 48 hours. 24 hours and 48 hours and are only analysed further. CONCLUSION In a review by Udani et al tuberculin testing using 1TU RT23 was positive in 52.3% (range 19.3-73.3%) of Tuberculin positivity is 3.5% in this study among children with tuberculosis.6 In present study, the children with symptoms suggestive of tuberculosis. positivity of the tuberculin skin test is 3.48% among 63.6% of Mantoux positive cases at 48 hours had >10 mm induration at 24 hours itself. Only 2.4% of cases had

International Journal of Contemporary Pediatrics | July-August 2017 | Vol 4 | Issue 4 Page 1238 Balasankar S et al. Int J Contemp Pediatr. 2017 Jul;4(4):1236-1239 no induration at 24 hours. Validity of reading Mantoux at 4. Pouchot J, Grasland A, Collet C, Coste J, Esdaile 24 hours instead of 48 hours have high specificity and JM, Vinceneux P. Reliability of tuberculin skin test PPV but low in sensitivity. Induration of >10 mm at 24 measurement. Ann Intern Med. 1997;126:210-21. hours will remain positive at 48 hours but <10 mm at 24 5. APIC Guidelines Committee. APIC position paper: hours has to be verified at 48 hours. There is no cut off responsibility for interpretation of the PPD value at 24 hours, that will suggest positivity (>10 mm) at tuberculin skin test. Am J Infect Control. 48 hours. 1999;27:56-8. 6. Udani PM. Evaluation of tuberculin test in pediatric Funding: No funding sources practice. Indian Pediatr. 1982;19:469-86. Conflict of interest: None declared 7. Serane VT, Nalini P, Mahadevan S. Predictive value Ethical approval: The study was approved by the of tuberculin induration at 24 h in healthy Institutional Ethics Committee of Government Rajaji schoolchildren. J tropical pediatrics. 2002;48(1):29- Hospital, Madurai, Tamil Nadu, India 32. 8. National Tuberculosis Institute, Bangalore. Bull REFERENCES WHO. 1974;51:473-487. 9. Oztwik P, Eskiocak M, Bay A, Sancak R, Dabak S, 1. Udani PM, Parthasarathy A. Tuberculosis in Gnrses N. Predictive value of a 24-hour tuberculin children. In: Parthasarathy A, Nair MKC, Menon skin test evaluation. Arch Dfs Child. 1997;76:452-3. rd PSN, eds. IAP Textbook of paediatrics. 3 ed. New delhi:Jaypee publishers;2006:206-20. 2. Chauhan LS, Arora VK. Management of pediatric Tuberculosis under the revised National Tuberculosis Control Programme. Indian J Pediatr. Cite this article as: Balasankar S, Balasubramanian 2004;71:341-3. J. A study on validity of reading Mantoux test at 24 3. World Health Organisation: The WHO standard hours. Int J Contemp Pediatr 2017;4:1236-9. tuberculin test, WHO/TB/Tech. Guide/3; 1963.

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